Technical Field
This disclosure relates to an injectable sustained release composition and a method of delivery of the same to reduce inflammation and to treat pain in joints, including pain caused by inflammatory diseases such as osteoarthritis or rheumatoid arthritis.
Description of the Related Art
Arthritis i.e., inflammation in the joints, consists of more than 100 different conditions which range from relatively mild forms of tendinitis and bursitis to crippling systemic forms, such as rheumatoid arthritis. It includes pain syndromes such as fibromyalgia and arthritis-related disorders, such as systemic lupus erythematosus, that involve every part of the body.
Generally, there are two types of arthritis:                Rheumatoid arthritis (“RA”) and related diseases, which are immune-mediated systemic inflammatory joint diseases.        Osteoarthritis (“OA”), which is a degenerative joint disease, the onset of which is typically mediated by previous joint injury or other factors.        
The common denominator for all of these arthritic conditions, including RA and OA is joint and musculoskeletal pain. Often this pain is a result of inflammation of the joint lining which is the body's natural response to injury. Such inflammation and pain can prevent the normal use and function of the joint. Pain and disability from arthritis, joint degeneration, and surgery are generally treated by a combination of oral medications or intra-articular injections of steroid compounds designed to reduce inflammation. In addition, other compositions, such as hyaluronic acid products, have been injected to provide visco-supplementation. A distinct benefit of a corticosteroid injection is that the relief of localized inflammation in a particular body area is more rapid and powerful than what can be achieved with traditional anti-inflammatory oral medications, such as aspirin. A single injection also can avoid certain side effects that can accompany multiple doses of oral anti-inflammatory medications, notably irritation of the stomach. Injections can be administered easily in a doctor's office. Other advantages include the rapid onset of the medication's action. Unfortunately, injections also have some systemic side effects or are not effective for extended periods of time.
Short-term complications are uncommon. Long-term risks of corticosteroid injections depend on the dose and frequency of the injections. With higher doses and frequent administration, potential side effects include thinning of the skin, easy bruising, weight gain, puffiness of the face, acne (steroid acne), elevation of blood pressure, cataract formation, thinning of the bones (osteoporosis), and a rare but serious type of damage to the bones of the large joints (avascular necrosis). Furthermore, there is an interdependent feedback mechanism between the hypothalamus, which is responsible for secretion of corticotrophin-releasing factor, the pituitary gland, which is responsible for secretion of adrenocorticotropic hormone, and the adrenal cortex, which secretes cortisol, termed the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis may be suppressed by the administration of corticosteroids, leading to a variety of unwanted side effects.
Accordingly, there is a medical need to extend the local duration of action of corticosteroids, while reducing the systemic side effects associated with that administration. In addition, there is a need for sustained local treatment of pain and inflammation, such as joint pain, with corticosteroids that results in clinically insignificant or no measurable HPA axis suppression. In addition, there is a medical need to slow, arrest, reverse or otherwise inhibit structural damage to tissues caused by inflammatory diseases such as damage to articular tissues resulting from osteoarthritis or rheumatoid arthritis.